This is an ongoing project aimed at developing sensitive non-invasive methods for studying fibrinogen catabolism in the human. Of particular significance has been the development of methodology for the study of the rate of fibrin formation in vivo. If fibrin formation rates lie within the physiological range, it is unlikely that the patient has a thrombotic lesion or suffers from intravascular coagulation. On the other hand if fibrin formation rates exceed the physiological rate the presence of thrombotic pathology or underlying intravascular coagulation is implied. Thus, knowledge of the rate of fibrin formation in vivo is helpful both in the prescription of antithromobotic drug therapy, but more important in judging its effectiveness. We have developed a procedure termed plasma fibrinogen chromatography that quantifies the percentage and concentration, in plasma, of high molecular weight of fibrinogen/fibrin complexes (HMWFC), native fibrinogen and derivatives of fibrinogen of smaller molecular weight than the native molecule (fibrinogen first derivative). Substantial clinical investigative data supports the concept that plasma HMWFC concentration reflects the rate of fibrin formation in vivo and that the concentration of fibrinogen first derivative the rate of fibrinogenolysis.